key: cord-0982651-khgwzeow authors: Drossinos, Yannis; Weber, Thomas P.; Stilianakis, Nikolaos I. title: Droplets and aerosols: An artificial dichotomy in respiratory virus transmission date: 2021-05-07 journal: Health Sci Rep DOI: 10.1002/hsr2.275 sha: 83741630a6003ac7ebc3ee068b737ef27715c208 doc_id: 982651 cord_uid: khgwzeow In the medical literature, three mutually non‐exclusive modes of pathogen transmission associated with respiratory droplets are usually identified: contact, droplet, and airborne (or aerosol) transmission. The demarcation between droplet and airborne transmission is often based on a cut‐off droplet diameter, most commonly 5 μm. We argue here that the infectivity of a droplet, and consequently the transmissivity of the virus, as a function of droplet size is a continuum, depending on numerous factors (gravitational settling rate, transport, and dispersion in a turbulent air jet, viral load and viral shedding, virus inactivation) that cannot be adequately characterized by a single droplet diameter. We propose instead that droplet and aerosol transmission should be replaced by a unique airborne transmission mode, to be distinguished from contact transmission. intermediate object (fomite) or person. Droplet transmission refers to transmission by large droplets (diameter d p > 5 μm) that are transported by the turbulent air flow generated by a violent expiratory event (coughing or sneezing). They are presumably sprayed and directly deposited upon the conjunctiva or mucus membranes of a susceptible host. Since large droplets deposit on environmental surfaces rather quickly by gravitational settling, droplet transmission is viewed to be important at close range: in still air, a 50 μm water droplet crosses a vertical 1.5 m distance in 20 seconds. 6 Airborne (or aerosol transmission) is defined as pathogen transmission via inhalation of small respiratory droplets (typically <5 μm: a 5 μm droplet settles gravitationally in still air within approximately 32 minutes). Given their small size they can deposit deep within the respiratory tract, including the alveolar region (see, eg, Vincent 7 or Drossinos and Housiadas 6 ). These droplets, often referred to as "droplet nuclei," are small enough to remain airborne sufficiently long to transmit the pathogen. Airborne transmission thus does not depend on direct face-to-face interactions. It is important to stress that droplet diameter is a dynamic quantity. Respiratory droplets are generated in a high relative humidity environment: upon expulsion, their diameter equilibrates by shrinking to the usually lower ambient relative humidity and temperature via water evaporation. Hygroscopic growth may also occur for a recently emitted droplet which, after partial evaporation, may encounter locally higher relative humidity or when the warm and humid exhaled air encounters colder environments. Evaporation and condensation, being molecular processes, are very fast, depending on the instantaneous droplet diameter. The evaporation time to reach the droplet equilibrium diameter varies from milliseconds for small droplets, for example, those of droplet diameters smaller than 10 μm, to seconds for larger droplets, for example, those greater than 100 μm. 8 Hence, even though the droplet diameter is a sensitive function of ambient conditions the relevant time scales are short (as is the gravitational settling time, see Reference 9 for an analysis of coupled evaporation and settling). A related topic of current research interest is the size of an equilibrated droplet, the final residue size. Respiratory droplets are aqueous droplets containing nonvolatile species like organic and inorganic salts, surfactants and proteins, and microbes. 10 The equilibrium droplet size and the evaporation rate depend on ambient conditions (temperature and humidity) as well as droplet properties, namely its chemical composition (presence of solutes) and droplet curvature (Kelvin effect). The combined effect of solute speciation and concentration (which decreases the droplet vapor pressure) and droplet curvature (which increases the droplet vapor pressure, but only becomes significant for diameters of aqueous droplets of less than approximately 0.5 μm) are collectively described by the Köhler curve. 11 An initial estimate of the equilibrated droplet size was that it shrinks to half its initial size. 10 More recent work considers the effect of droplet chemical composition (pure water with added salt and added glycoprotein [mucin] and surfactant) to find that the equilibrated diameter may be less than half the initial diameter. 12, 13 For pure saliva droplets the final droplet size was estimated to be about 20% of the initial droplet size for a variety of ambient conditions. 14 Given the importance of the droplet size in determining its transport and deposition properties, 6 the effect of respiratory-droplet composition on the final droplet size could become an important direction for future work. Herein, all droplet diameters are taken to be the locally equilibrated diameters, unless otherwise stated. We contend that the received view of transmission modes becomes increasingly difficult to sustain in light of new experimental, empirical, and theoretical findings. In our view, the demarcation between the three transmission modes is arbitrary, and especially the distinction between droplet and aerosol transmission is not tenable any longer as it is not based on well-defined physical properties of droplets or their dynamics in a complex physical environment. For example, current estimates of large-droplet dispersion suggest that the exhaled buoyant turbulent flow may transport them to considerable distances (larger than 1 or 2 m) where they may be inhaled instead of directly deposited on an individual's face, that is, large droplets usually associated with what is referred to in the biomedical literature as droplet transmission may behave as what is referred to as aerosols. We argue here for a view that describes modes of transmission as a continuum based on physical properties of exhaled droplets and their interactions with the environment and human behavior. A similar idea was recently proposed by Bahl et al. 15 We question this sharp dichotomy in that it considers the droplet diameter, through its effect on the droplet airborne lifetime, a good, in fact the only, proxy for the airborne transmissibility of the pathogen. It neglects that the infectious agent is the pathogen within the airborne droplet, not the droplet itself. This realization implies that other physical, biological, even behavioral effects, should be considered in a proper description of the transmission pathways. An early attempt, 16 summarized in Reference, 17 to quantify these processes and to com- suggests that droplet diameter is not sufficient to determine the infectivity of a droplet, and that at least viral shedding should be incorporated in the estimate, that is, the total emitted viral load per, for example, minute of speaking or per cough or sneeze should be considered. Several biological processes affect the infectious airborne lifetime and infection probability. Droplet shedding, through the mechanism that induces an expiratory event, viral load (through the viral concentration in the respiratory-tract regions), minimum infectious dose, and virus inactivation contribute to the infectivity of a droplet. The 5 μm demarcation neglects these significant contributions to the infectivity of a droplet. Higher viral load was associated with symptomatic infected patients compared to asymptomatic. 41, 42 Patients with lower respiratory tract clinical symptoms had higher viral loads than those with upper respiratory tract infection. Viral shedding lasts longer in hospitalized patients. 43 This pattern may differ among respiratory infections and shows some variability between asymptomatic and symptomatic persons with the symptomatic being predominantly those with higher viral loads and viral shedding. 44 Higher viral dose has been associated with the development of symptoms. 45, 46 Virus inactivation is another major determinant of airborne infec- related to, in particular, meatpacking plants 57, 58 illustrate this risk connected to certain dry and cold indoor environments. The above considerations establish, in our view, the mechanistic basis Models are sensitive to unmeasured or difficult to measure parameters such as viral load and droplet shedding. 64 However, valuable epidemiological evidence to assess better the relative importance of these modes and to uncover the potentially important, and currently underestimated, airborne transmission mode is increasing. 62, 65 For example, the previously mentioned works on droplet transport and dispersion emphasize the importance of an external air flow, as We suggest that the traditional distinction between droplet-nuclei (or aerosol or airborne) and large-droplet transmission is no longer tenable in view of the extensive theoretical and experimental work on respiratory droplets. It is our view that it should be replaced by a unique non-contact airborne transmission mode, a transmission mode distinct from contact transmission. This suggestion would also help to quell the sometimes vehement arguments over "aerosolization," that is whether small droplet (d p < 5 μm) transmission is a significant mode of transmission of SARS-CoV-2 (see, eg, the recent arguments in Peters et al. 67 and the reply in Dancer et al. 37 ). One of the distinguishing features of SARS-CoV-2 is its long incubation period that consists of a latent period and the subsequent appearance of asymptomatic infections from which transmission can arise. Some of them recover without ever developing identifiable symptoms, while others will develop clinical symptoms. Violent expiratory events (coughing and sneezing) are associated with infected individuals with clinical symptoms. Asymptomatic individuals, however, contribute to viral spreading via normal respiratory activities: breathing, speaking, laughing, singing, and light coughs. In addition, their behavior remains unchanged, retaining the same average daily contacts and contact times with other individuals. It is, therefore, of great importance to understand the droplet shedding (and the associated viral load and airborne lifetimes of the emitted infectious droplets), and behavioral/social characteristics of these two groups, especially since it is currently believed that asymptomatic infectious individuals, whether on the way to develop symptoms or not, might make a substantial contribution to the transmission of SARS-CoV-2. The work reviewed here suggests that the range and duration in which airborne droplets pose a significant infection risk for influenza A and SARS-CoV-2 may have been significantly underestimated. As a consequence, recommendations on the use of N95 or surgical masks or on spatial separation should be continuously reviewed in light of the emerging findings on the biophysics of airborne droplets. Given that, as argued here, the infectivity of a droplet, and consequently, the transmissivity of the virus, as a function of droplet size is a continuum, recommendations to always wear facemasks in indoor public areas, even if a spatial separation of at least 1 to 2 m can be observed, are, in our view, justified. The authors thank Walter J. Hugentobler, MD, for valuable discussions and helpful comments on the manuscript. The authors declare there is no conflict of interest. Conceptualization: Yannis Drossinos, Thomas P. Weber, Nikolaos Investigation: Yannis Drossinos, Thomas P. Weber, Nikolaos Writing-original draft preparation: Yannis Drossinos, Thomas P. Weber, Nikolaos I. Stilianakis Writing-review and editing: Yannis Drossinos, Thomas P. Weber, All authors have read and approved the final version of the manuscript. Nikolaos I. Stilianakis affirms that this manuscript is an honest, accurate, and transparent account of the study being reported and that no important aspects of the study have been omitted. The views expressed in this article are purely those of the authors and may not, under any circumstances, be regarded as an official position of the European Commission. Data sharing is not applicable to this article as no new data were created or analyzed in this study. https://orcid.org/0000-0002-8059-9636 Thomas P. Weber https://orcid.org/0000-0002-4723-4950 Nikolaos I. Stilianakis https://orcid.org/0000-0002-3808-265X Transmission of influenza a in human beings Inactivation of influenza A viruses in the environment and modes of transmission: a critical review Visualization of sneeze ejecta: steps of fluid fragmentation leading to respiratory droplets Exhaled respiratory particles during singing and talking Guideline for isolation precautions: preventing transmission of infectious agents in health care settings Aerosol flows Health-related aerosol measurement: a review of existing sampling criteria and proposals for new ones The impact of ambient humidity on the evaporation and dispersion of exhaled breathing droplets: a numerical investigation Accurate representation of the microphysical processes occurring during the transport of exhaled aerosols and droplets Toward understanding the risk of secondary airborne infection: emission of respirable pathogens Aerosol Technology: Properties, Behaviour, and Measurement of Airborne Particles Evolution of spray and aerosol from respiratory releases: theoretical estimates for insight on viral transmission Physico-chemical characteristics of evaporating respiratory droplets Insights into the evaporation characteristics of saliva droplets and aerosols: levitation experiments and numerical modeling Airborne or droplet precautions for health workers treating corona virus disease 2019? Dynamics of infectious disease transmission by inhalable respiratory droplets What aerosol physics tells us about airborne pathogen transmission The flow physics of COVID-19 On air-borne infection-study ii. Droplets and droplet nuclei How far droplets can move in indoor environments-revisiting the Wells evaporation-falling curve Airborne Transmission of SARS-CoV-2: Proceedings of a Workshop in Brief On coughing and airborne droplet transmission to humans Transport and fate of human expiratory droplets-a modeling approach Violent expiratory events: on coughing and sneezing Turbulent gas clouds and respiratory pathogen emissions Study on transport characteristics of saliva droplets produced by coughing in a calm indoor environment Influence of wind and relative humidity on the social distancing effectiveness to prevent COVID-19 airborne transmission: a numerical study The size and the duration of air-carriage of respiratory droplets and droplet-nuclei Relation between the airborne diameters of respiratory droplets and the diameter of the stains left after recovery Aerosol emission and superemission during human speech increase with voice loudness The coronavirus pandemic and aerosols: does COVID-19 transmit via expiratory particles? Modality of human expired aerosol distributions Size distribution and sites of origin of droplets expelled from the human respiratory tract during expiratory activities Size-distribution dependent lung deposition of diesel exhaust particles Deposition of droplets from the trachea or bronchus in the respiratory tract during exhalation: a steady-state numerical investigation The infectious nature of patient-generated SARS-CoV-2 aerosol The airborne lifetime of small speech droplets and their potential importance in SARS-CoV-2 transmission Modeling the load of SARS-CoV-2 virus in human expelled particles during coughing and speaking Viral shedding and transmission potential of asymptomatic and paucisymptomatic influenza virus infections in the community Viral dynamics in mild and severe cases of COVID-19 Correlation of pandemic (H1N1) 2009 viral load with disease severity and prolonged viral shedding in children Temporal dynamics in viral shedding and transmissibility of COVID-19 A dose-finding study of a wild-type influenza A(H3N2) virus in a healthy volunteer human challenge model Validation of the wild-type influenza A human challenge model H1N1pdMIST: an A(H1N1) pdm09 dose-finding investigational new drug study The influence of temperature, humidity and simulated sunlight on the infectivity of SARS-CoV-2 in aerosols Influenza virus infectivity is retained in aerosols and droplets independent of relative humidity Mechanistic insights into the effect of humidity on airborne influenza virus survival, transmission and incidence Inactivation of airborne influenza virus in the ambient air Absolute humidity modulates influenza survival, transmission, and seasonality Experimental aerosol survival of SARS-CoV-2 in artificial saliva and tissue culture media at medium and high humidity Aerosol and surface stability of SARS-CoV-2 compared to SARS-CoV-1 Relationship between humidity and influenza A viability in droplets and implications for influenza's seasonality Estimated inactivation of corona viruses by solar radiation with special reference to COVID-19. Photochem Photobiol Airborne SARS-COV-2 is rapidly inactivated by simulated sunlight COVID-19 among workers in meat and poultry processing facilities-19 States High COVID-19 attack rate among attendees at events at a church-Arkansas Aerosol transmission is an important mode of influenza A virus spread Relative contributions of four exposure pathways to influenza infection risk Spatial dynamics of airborne infectious diseases Infectious virus in exhaled breath of symptomatic seasonal influenza case from a college community Relative contributions of transmission routes for COVID-19 among healthcare personnel providing patient care COVID-19 patients in earlier stages exhaled millions of SARS-CoV-2 per hour Community outbreak investigation of SARS-CoV-2 transmission among bus riders in eastern China Transmission of SARS-CoV-2 by inhalation of respiratory aerosol in the Skagit Valley Chorale superspreading event Putting some context to the debate around SARS-COV-2 Droplets and aerosols: An artificial dichotomy in respiratory virus transmission